Structural members for prosthetic mitral valves

ABSTRACT

A self-expanding wire frame for a pre-configured compressible transcatheter prosthetic cardiovascular valve, a combined inner frame/outer frame support structure for a prosthetic valve, and methods for deploying such a valve for treatment of a patient in need thereof, are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/472,935, filed on Mar. 29, 2017, which is a continuation of U.S.patent application Ser. No. 14/950,656, filed Nov. 24, 2015 and issuedas U.S. Pat. No. 9,610,159 on Apr. 4, 2017, which is a continuation ofInternational Application No. PCT/US2014/040188, filed May 30, 2014,which claims priority to and is a continuation-in-part of U.S. patentapplication Ser. No. 14/155,417, filed Jan. 15, 2014, which claimspriority to and the benefit of U.S. Provisional Application No.61/829,076, filed May 30, 2013. International Application No.PCT/US2014/040188 also claims priority to and the benefit of U.S.Provisional Application No. 61/829,076, filed May 30, 2013. Each of theforegoing disclosures is hereby incorporated by reference in itsentirety.

BACKGROUND Field of Invention

An improved transcatheter prosthetic heart valve includes structuralmembers, such as in the form of wire frames, which provide support forthe valve and aid in reducing or preventing leakage.

Background

Valvular heart disease and specifically aortic and mitral valve diseaseis a significant health issue in the US. Annually approximately 90,000valve replacements are conducted in the US. Traditional valvereplacement surgery, the orthotopic replacement of a heart valve, is an“open heart” surgical procedure. Briefly, the procedure necessitates asurgical opening of the thorax, initiation of extra-corporealcirculation with a heart-lung machine, stopping and opening the heart,excision and replacement of the diseased valve, and re-starting of theheart. While valve replacement surgery typically carries a 1-4%mortality risk in otherwise healthy persons, a significantly highermorbidity is associated to the procedure, largely due to the necessityfor extra-corporeal circulation. Further, open heart surgery is oftenpoorly tolerated in elderly patients.

Thus if the extra-corporeal component of the procedure could beeliminated, morbidities and cost of valve replacement therapies would besignificantly reduced.

While replacement of the aortic valve in a transcatheter manner is thesubject of intense investigation, lesser attention has been focused onthe mitral valve. This is in part reflective of the greater level ofcomplexity associated to the native mitral valve apparatus and thus agreater level of difficulty with regards to inserting and anchoring thereplacement prosthesis.

Various problems exist in this field, including problems of insufficientarticulation and sealing of the valve within the native annulus,pulmonary edema due to poor atrial drainage, perivalvular leaking aroundthe installed prosthetic valve, lack of a good fit for the prostheticvalve within the native mitral annulus, atrial tissue erosion, excesswear on the valve structures, interference with the aorta at theposterior side of the mitral annulus, and lack of customization, to namea few. Accordingly, there is still a need for an improved prostheticmitral valve.

SUMMARY

Apparatus, systems, and methods include a self-expanding wire frames fora prosthetic cardiovascular valve. The prosthetic cardiovascular valveincludes a cylindrical framework defining a lumen. The cylindricalframework includes multiple generally diamond-shaped members. Eachdiamond-shaped member defines multiple lateral vertices and multiplelongitudinal vertices. Each diamond-shaped member is coupled to one ormore other diamond-shaped members. Each coupling can be at or about eachof the lateral vertices of the diamond-shaped member.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded view of a prosthetic cardiovascular valveaccording to an embodiment.

FIG. 2 is an oblique projection of a three-diamond self-expanding wireframe as a cylindrical frame defining a lumen according to anembodiment.

FIG. 3 is a perspective side view of a three-diamond self-expanding wireframe as a cylindrical frame defining a lumen according to anotherembodiment.

FIG. 4 is an opened and flattened view of a three-diamond cylindricalframe showing the detail of wire rods, multiple spanning rods, andvertices, according to another embodiment.

FIG. 5 is an opened and flattened view of an open-V cylindrical frameshowing the detail of wire rods, and vertices, according to anotherembodiment.

FIG. 6 is an opened and flattened view of a three-diamond cylindricalframe showing the detail of wire rods, spanning rods, and vertices,according to another embodiment.

FIG. 7 is an oblique projection of a four-diamond self-expanding wireframe as a cylindrical frame defining a lumen, according to anotherembodiment.

FIG. 8 is an opened and flattened view of a four-diamond cylindricalframe showing the detail of wire rods, multiple spanning rods, andvertices, according to another embodiment.

FIG. 9 is an opened and flattened view of an open-V cylindrical frameshowing the detail of wire rods, and vertices, according to anotherembodiment.

FIG. 10 is an opened and flattened view of a four-diamond cylindricalframe showing the detail of wire rods, spanning rods, and vertices,according to another embodiment.

FIG. 11 is an oblique projection view of a three-square cylindricalframe showing the detail of wire rods, multiple spanning rods, andvertices, according to another embodiment.

FIG. 12 is an opened and flattened view of the frame of FIG. 11 .

FIG. 13 is an exploded view of a prosthetic cardiovascular valveaccording to another embodiment.

FIGS. 14A-14C show initial, partially expanded, and fully expandedstates of an outer frame according to an embodiment.

FIG. 15 is an exploded view of a prosthetic cardiovascular valveaccording to another embodiment.

FIG. 16 is an opened and flattened view of an unexpanded inner wireframestructure, according to an embodiment.

FIGS. 17 and 18 are side and bottom views, respectively, of the innerwireframe structure of FIG. 16 in an expanded configuration.

FIG. 19 is an opened and flattened view of an unexpanded outer frameaccording to an embodiment.

FIGS. 20 and 21 are side and top views, respectively, of the outer frameof FIG. 19 in an expanded configuration.

FIGS. 22-24 are side, front, and top views of an assembly of the innerwireframe structure of FIGS. 16-18 and the outer frame of FIGS. 19-21 ,forming a support structure for a prosthetic valve, according to anembodiment.

DETAILED DESCRIPTION

FIG. 1 is an exploded view of one embodiment of a pre-configuredcompressible transcatheter prosthetic cardiovascular valve 10. In thisembodiment, valve 10 includes an inner structure or assembly 12, and anouter structure or assembly 14. Valve 10 may be coupled to a tether 160,and a tether anchor 154.

Inner assembly 12 includes a self-expanding frame 100, an outercylindrical wrap 152 disposed about the inner wire frame (to acts as acover to prevent valvular leakage) and a leaflet structure 136(comprised of articulating leaflets 138 that define a valve function).The leaflet structure 136 may be sewn to the inner wireframe 100. Thewireframe 100 also has (tether) attachment apertures 111 to which thetether 160 can be attached. Tether 160 is connected to tether anchor154, which in this embodiment is implemented as an epicardial securingpad.

Outer assembly 14 includes an outer stent or frame 144, an outer cover150, and a cuff covering 148. In this embodiment, outer frame 144 has aflared, articulating collar or cuff 146 over which the cuff covering 148is disposed. Cuff 146 has a D-shaped section 162 to accommodate andsolve left ventricular outflow tract (LVOT) obstruction issues.

Cuff 146 may be configured a substantially flat plate that projectsbeyond the diameter of the tubular body of outer frame 144 to form a rimor border. The terms flared end, cuff, flange, collar, bonnet, apron, orskirting used interchangeable herein. When the tubular body of frame 144is pulled through the aperture of a mitral valve aperture, the mitralannulus, such as by tether loops, in the direction of the leftventricle, the cuff acts as a collar to stop the frame from travelingany further through the mitral valve aperture. The entire prostheticvalve is held by longitudinal forces between the cuff, which is seatedin the left atrium and mitral annulus, and the ventricular tethersattached to the left ventricle.

Cuff 146 may be formed from a stiff, flexible shape-memory material suchas the nickel-titanium alloy material Nitinol® formed as wire, andcovered by cuff covering 148, which may be formed of stabilized tissueor other suitable biocompatible or synthetic material. In oneembodiment, the cuff is constructed from independent articulating radialtines or posts of wire extending axially around the circumference of thebend or seam where cuff 146 transitions to the tubular body of frame 144(in an integral flared end or cuff) or where cuff 146 is attached to theframe body (in an implementation in which they are separate, but joinedcomponents).

With cuff cover 148 in place articulating radial tines or posts of wireprovide the cuff the ability to move up and down, to articulate, alongthe longitudinal axis that runs through the center of frame 144. Inother words, the individual articulating radial tines or posts of wirecan independently move up and down, and can spring back to theiroriginal position due to the relative stiffness of the wire. The tissueor material that covers the cuff wire has a certain modulus ofelasticity such that, when attached to the wire of the cuff, is able toallow the wire spindles to move. This flexibility gives the cuff, uponbeing deployed within a patient's heart, the ability to conform to theanatomical shape necessary for a particular application. In the exampleof a prosthetic mitral valve, the cuff is able to conform to theirregularities of the left atrium and shape of the mitral annulus, andto provide a tight seal against the atrial tissue adjacent the mitralannulus and the tissue within the mitral annulus. As stated previously,this feature provides a degree of flexibility in sizing the mitral valveand prevents blood from leaking around the implanted prosthetic heartvalve.

An additional aspect of the cuff dimension and shape is that, when fullyseated and secured, the edge of the cuff preferably should not beoriented laterally into the atrial wall, in which orientation it mightproduce a penetrating or cutting action on the atrial wall.

In some embodiments, the wire spindles of the cuff are substantiallyuniform in shape and size. In some embodiments, each loop or spindle maybe of varying shapes and sizes. In this example, it is contemplated thatthe articulating radial tines or posts of wire may form a pattern ofalternating large and small articulating radial tines or posts of wire,depending on where the valve is being deployed. In the case of aprosthetic mitral valve, pre-operative imaging may allow for customizingthe structure of the cuff depending on a particular patient's anatomicalgeometry in the vicinity of the mitral annulus.

The cuff is constructed so as to provide sufficient structural integrityto withstand the intracardiac forces without collapsing.

Inner frame 100 and outer frame or frame 144, including cuff 146, arepreferably formed to be deformed (compressed and/or expanded) and, whenreleased, return to their original (undeformed) shapes. To achieve this,the components are preferably formed of materials, such as metals orplastics, that have shape memory properties. With regards to metals,Nitinol® has been found to be especially useful since it can beprocessed to be austenitic, martensitic or super elastic. Martensiticand super elastic alloys can be processed to demonstrate the requiredcompression features. Thus, inner frame 100 and outer frame or frame144, including cuff 145, are preferably constructed of Nitinol®, and arecapable of maintaining their functions while under longitudinal forcesthat might cause a structural deformation or valve displacement. Othershape memory alloys, such as Cu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys,may be used.

Inner frame 100 and outer frame or frame 144, including cuff 146, arepreferably formed from a laser cut, thin-walled tube of Nitinol® Thelaser cuts form regular cutouts in the thin Nitinol® tube. Secondarilythe tube is placed on a mold of the desired shape, heated to themartensitic temperature and quenched. The treatment of the frame in thismanner will form a flared end or cuff that has shape memory propertiesand will readily revert to the memory shape at the calibratedtemperature.

Alternatively, these components may be constructed from braided wire

The cuff provides several functions. The first function is to inhibitperivalvular leakage and regurgitation of blood around the prosthesis.By flexing and sealing across the irregular contours of the annulus andatrium, leakage is minimized or prevented.

The second function of the cuff is to provide an adjustable and/orcompliant bioprosthetic valve. The heart and its structures undergocomplex conformational changes during the cardiac cycle. For example,the mitral valve annulus has a complex geometric shape known as ahyperbolic paraboloid that is shaped like a saddle, with the horn beinganterior, the seat back being posterior, and the left and right valleyslocated medially and laterally. Beyond this complexity, the area of themitral annulus changes over the course of the cardiac cycle. Further,the geometry of the tricuspid valve and tricuspid annulus continues tobe a topic of research, posing its own particular problems. Accordingly,compliance is a very important but unfortunately often overlookedrequirement of cardiac devices. Compliance here refers to the ability ofthe valve to change conformation with the native annulus in order tomaintain structural position and integrity throughout the cardiac cycle.Compliance with the motion of the heart is a particularly usefulfeature, especially the ability to provide localized compliance wherethe underlying surfaces are acting differently from the adjacentsurfaces. This ability to vary throughout the cardiac cycle allows thevalve to remain seated and properly deployed in a manner not heretoforeprovided.

Additionally, compliance may be achieved through the use of the tetherswhere the tethers are preferably made from an elastic material.Tether-based compliance may be used alone, or in combination with thecuff-based compliance.

The third function of the cuff is to enable the valve, duringimplantation surgery, to conform to the irregular surfaces of theatrium. This function can be enhanced by the use of independent tethers,allowing for side-to-side fitting of the valve within the annulus. Forexample, where three tethers are used, they can be spacedcircumferentially about 120 degrees relative to each other, which allowsthe surgeon to observe whether or where perivalvular leaking might beoccurring and to pull on one side or the other to create localizedpressure and reduce or eliminate the leakage.

The fourth function of the cuff is to counter the forces that act todisplace the prosthesis toward/into the ventricle (i.e. atrial pressureand flow-generated shear stress) during ventricular filling.

The heart is known to generate an average left atrial pressure betweenabout 8 and 30 mm Hg (about 0.15 to 0.6 psi). This left atrial fillingpressure is the expected approximate pressure that would be exerted inthe direction of the left ventricle when the prosthesis is open againstthe outer face of the flared end or cuff as an anchoring force holdingthe flared end or cuff against the atrial tissue that is adjacent themitral valve. Cuff 146 counteracts this longitudinal pressure againstthe prosthesis in the direction of the left ventricle to keep the valvefrom being displaced or slipping into the ventricle. In contrast, leftventricular systolic pressure, normally about 120 mm Hg, exerts a forceon the closed prosthesis in the direction of the left atrium. Thetethers counteract this force and are used to maintain the valveposition and withstand the ventricular force during ventricularcontraction or systole. Accordingly, cuff 146 has sufficient structuralintegrity to provide the necessary tension against the tethers withoutbeing dislodged and pulled into the left ventricle. After a period oftime, changes in the geometry of the heart and/or fibrous adhesionbetween prosthesis and surrounding cardiac tissues may assist or replacethe function of the ventricular tethers in resisting longitudinal forceson the valve prosthesis during ventricular contraction.

Additional features of the cuff include that it functions to strengthenthe leaflet assembly/frame complex by providing additional structure.Further, during deployment, the cuff functions to guide the entirestructure, the prosthetic valve, into place at the mitral annulus duringdeployment and to keep the valve in place once it is deployed. Anotherimportant function is to reduce pulmonary edema by improving atrialdrainage.

The valve leaflets are held by, or within, a leaflet assembly. In someembodiments, the leaflet assembly comprises a leaflet wire supportstructure to which the leaflets are attached and the entire leafletassembly is housed within the frame body. In this embodiment, theassembly is constructed of wire and stabilized tissue to form a suitableplatform for attaching the leaflets. In this aspect, the wire andstabilized tissue allow for the leaflet structure to be compressed whenthe prosthetic valve is compressed within the deployment catheter, andto spring open into the proper functional shape when the prostheticvalve is opened during deployment. In this embodiment, the leafletassembly may optionally be attached to and housed within a separatecylindrical liner made of stabilized tissue or material, and the lineris then attached to line the interior of the frame body.

In this embodiment, the leaflet wire support structure is constructed tohave a collapsible/expandable geometry. In some embodiments, thestructure is a single piece of wire. The wireform is, in one embodiment,constructed from a shape memory alloy such as Nitinol®. The structuremay optionally be made of a plurality of wires, including between 2 to10 wires. Further, the geometry of the wire form is without limitation,and may optionally be a series of parabolic inverted collapsible archesto mimic the saddle-like shape of the native annulus when the leafletsare attached. Alternatively, it may optionally be constructed ascollapsible concentric rings, or other similar geometric forms, each ofwhich is able to collapse or compress, then expand back to itsfunctional shape. In some embodiments, there may be 2, 3 or 4 arches. Inanother embodiment, closed circular or ellipsoid structure designs arecontemplated. In another embodiment, the wire form may be anumbrella-type structure, or other similar unfold-and-lock-open designs.In some embodiments utilizes super elastic Nitinol® wire approximately0.015″ in diameter. In this embodiment, the wire is wound around ashaping fixture in such a manner that 2-3 commissural posts are formed.The fixture containing the wrapped wire is placed in a muffle furnace ata pre-determined temperature to set the shape of the wire form and toimpart its super elastic properties. Secondarily, the loose ends of thewireform are joined with a stainless steel or Nitinol® tube and crimpedto form a continuous shape. In some embodiments, the commissural postsof the wireform are adjoined at their tips by a circular connectingring, or halo, whose purpose is to minimize inward deflection of thepost(s).

In some embodiments, the leaflet assembly is constructed solely ofstabilized tissue or other suitable material without a separate wiresupport structure. The leaflet assembly in this embodiment is alsodisposed within the lumen of the frame and is attached to the frame toprovide a sealed joint between the leaflet assembly and the inner wallof the frame. By definition, it is contemplated within the scope of theinvention that any structure made from stabilized tissue and/or wire(s)related to supporting the leaflets within the frame constitute a leafletassembly. In this embodiment, stabilized tissue or suitable material mayalso optionally be used as a liner for the inner wall of the frame andis considered part of the leaflet assembly.

Liner tissue or biocompatible material may be processed to have the sameor different mechanical qualities, such as thickness, durability, etc.,from the leaflet tissue.

Multiple types of tissue and biocompatible material may be used to coverthe cuff, to form the valve leaflets, to form a wireless leafletassembly, and/or to line both the inner and/or outer lateral walls ofouter frame 144. As stated previously, the leaflet component may beconstructed solely from stabilized tissue, without using wire, to createa leaflet assembly and valve leaflets. In this aspect, the tissue-onlyleaflet component may be attached to the frame with or without the useof the wire form. In some embodiments, there can be anywhere from 1, 2,3 or 4 leaflets, or valve cusps.

The tissue may be used to cover the inside of the frame body, theoutside of the frame body, and the top and/or bottom side of the cuffwire form, or any combination thereof.

In some embodiments, the tissue used herein is optionally a biologicaltissue and may be a chemically stabilized valve of an animal, such as apig. In some embodiments, the biological tissue is used to make leafletsthat are sewn or attached to a metal frame. This tissue is chemicallystabilized pericardial tissue of an animal, such as a cow (bovinepericardium) or sheep (ovine pericardium) or pig (porcine pericardium)or horse (equine pericardium).

Preferably, the tissue is bovine pericardial tissue. Examples ofsuitable tissue include that used in the products Duraguard®,Peri-Guard®, and Vascu-Guard®, all products currently used in surgicalprocedures, and which are marketed as being harvested generally fromcattle less than 30 months old.

In some embodiments, the valve leaflets may optionally be made from asynthetic material such as polyurethane or polytetrafluoroethylene.Where a thin, durable synthetic material is contemplated, e.g. forcovering the flared end or cuff, synthetic polymer materials suchexpanded polytetrafluoroethylene or polyester may optionally be used.Other suitable materials may optionally include thermoplasticpolycarbonate urethane, polyether urethane, segmented polyetherurethane, silicone polyether urethane, silicone-polycarbonate urethane,and ultra-high molecular weight polyethylene. Additional biocompatiblepolymers may optionally include polyolefins, elastomers,polyethylene-glycols, polyethersulphones, polysulphones,polyvinylpyrrolidones, polyvinylchlorides, other fluoropolymers,silicone polyesters, siloxane polymers and/or oligomers, and/orpolylactones, and block co-polymers using the same.

In another embodiment, the valve leaflets may optionally have a surfacethat has been treated with (or reacted with) an anti-coagulant, such as,without limitation, immobilized heparin. Such currently availableheparinized polymers are known and available to a person of ordinaryskill in the art.

Alternatively, the valve leaflets may optionally be made frompericardial tissue or small intestine submucosal tissue.

In another embodiment, the prosthetic valve is sized and configured foruse in areas other than the mitral annulus, including, withoutlimitation, the tricuspid valve between the right atrium and rightventricle. Alternative embodiments may optionally include variations tothe flared end or cuff structure to accommodate deployment to thepulmonary valve between the right ventricle and pulmonary artery, andthe aortic valve between the left ventricle and the aorta. In oneembodiment, the prosthetic valve is optionally used as a venous backflowvalve for the venous system, including without limitation the vena cava,femoral, subclavian, pulmonary, hepatic, renal and cardiac. In thisaspect, the flared end or cuff feature is utilized to provide additionalprotection against leaking.

As shown in FIG. 1 , tether 160 may be attached to valve 10. Tether 160(which may include multiple tethers) may extend to one or more tissueanchor locations within the heart. In some embodiments, the tether(s)extends downward through the left ventricle, exiting the left ventricleat the apex of the heart to be fastened on the epicardial surfaceoutside of the heart. Similar anchoring is contemplated herein as itregards the tricuspid, or other valve structure requiring a prosthetic.There may be from 1 to 8, or more, tethers.

In some embodiments, the tether(s) may optionally be attached to thecuff to provide additional control over position, adjustment, andcompliance. In some embodiments, one or more tethers are optionallyattached to the cuff, in addition to, or optionally, in place of, thetethers attached to the outer frame 144. By attaching to the cuff and/orthe frame, an even higher degree of control over positioning,adjustment, and compliance is provided to the operator duringdeployment.

During deployment, the operator is able to adjust or customize thetethers to the correct length for a particular patient's anatomy. Thetether(s) also allows the operator to tighten the cuff onto the tissuearound the valvular annulus by pulling the tether(s), which creates aleak-free seal.

In some embodiments, the tether(s) is optionally anchored to othertissue location(s) depending on the particular application of valve 10.In the case of a mitral valve, or the tricuspid valve, one or moretethers are optionally anchored to one or both papillary muscles,septum, and/or ventricular wall.

In some embodiments, the ventricular end of outer frame 144, or of innerframe 100, comes to 2-5 points onto which anchoring sutures or tetherare affixed. The tethers will traverse the ventricle and ultimately beanchored to the epicardial surface of the heart approximately at thelevel of the apex. The tethers when installed under slight tension willserve to hold the valve in place, i.e. inhibit perivalvular leakageduring systole.

The tethers, in conjunction with the cuff, provide greater compliancefor the valve. The tethers may be made from surgical-grade materialssuch as biocompatible polymer suture material. Non-limiting examples ofsuch material include ultra high-molecular weight polyethylene (UHMWPE),2-0 exPFTE (polytetrafluoroethylene) or 2-0 polypropylene. In oneembodiment the tethers are inelastic. One or more of the tethers mayoptionally be elastic to provide an even further degree of compliance ofthe valve during the cardiac cycle. Upon being drawn to and through theapex of the heart, the tethers may be fastened by a suitable mechanismsuch as tying off to a pledget or similar adjustable button-typeanchoring device to inhibit retraction of the tether back into theventricle. It is also contemplated that the tethers might bebioresorbable/bioabsorbable and thereby provide temporary fixation untilother types of fixation take hold such a biological fibrous adhesionbetween the tissues and prosthesis and/or radial compression from areduction in the degree of heart chamber dilation.

Valve 10 may optionally be deployed with a combination of installationtethers and permanent tethers, attached to outer frame 144, and/or cuff146, and/or inner frame 100, the installation tethers being removedafter the valve is successfully deployed. It is also contemplated thatcombinations of inelastic and elastic tethers may optionally be used fordeployment and to provide structural and positional compliance of thevalve during the cardiac cycle.

Valve 10 may be deployed as a prosthetic mitral valve using catheterdelivery techniques. The entire valve 10 is compressed within a narrowcatheter and delivered to the annular region of the native valve,preferably the left atrium, with a pre-attached tether apparatus. There,the valve 10 is pushed out of the catheter where it springs open intoits pre-formed functional shape without the need for manual expansionusing an inner balloon catheter. When the valve 10 is pulled into place,the outer frame 144 is seated in the native mitral annulus, leaving thecuff 146 to engage the atrial floor and prevent pull-through (where thevalve is pulled into the ventricle). The native leaflets are notcut-away as has been taught in prior prosthetic efforts, but are used toprovide a tensioning and sealing function around the outer frame 144.The valve 10 is preferably deployed asymmetrically to address LVOTproblems, unlike non-accommodating prosthetic valves that push againstthe A2 anterior segment of the mitral valve and close blood flow throughthe aorta, which anatomically sits immediately behind the A2 segment ofthe mitral annulus. Thus, D-shaped section 162 is preferably deployedimmediately adjacent/contacting the A2 segment since the flattenedD-shaped section 162 is structurally smaller and has a more verticalprofile (closer to paralleling the longitudinal axis of the outer frame)and thereby exerts less pressure on the A2 segment. Once valve 10 isproperly seated, tether 160 may be extended out through the apicalregion of the left ventricle and secured using an epicardial pad 154 orsimilar suture-locking attachment mechanism.

Valve 10 is, in one embodiment, apically delivered through the apex ofthe left ventricle of the heart using a catheter system. In one aspectof the apical delivery, the catheter system accesses the heart andpericardial space by intercostal delivery. In another delivery approach,the catheter system delivers valve 10 using either an antegrade orretrograde delivery approach using a flexible catheter system, andwithout requiring the rigid tube system commonly used. In anotherembodiment, the catheter system accesses the heart via a trans-septalapproach.

In some embodiments, the frame body extends into the ventricle about tothe edge of the open mitral valve leaflets (approximately 25% of thedistance between the annulus and the ventricular apex). The open nativeleaflets lay against the outside frame wall and parallel to the longaxis of the frame (i.e. the frame holds the native mitral valve open).

In some embodiments, the diameter should approximately match thediameter of the mitral annulus. Optionally, the valve may be positionedto sit in the mitral annulus at a slight angle directed away from theaortic valve such that it is not obstructing flow through the aorticvalve. Optionally, the outflow portion (bottom) of the frame should notbe too close to the lateral wall of the ventricle or papillary muscle asthis position may interfere with flow through the prosthesis. As theseoptions relate to the tricuspid, the position of the tricuspid valve maybe very similar to that of the mitral valve.

In one embodiment, to control the potential tearing of tissue at theapical entry point of the delivery system, a circular, semi-circular, ormulti-part pledget may be employed. The pledget may be constructed froma semi-rigid material such as PTFE felt. Prior to puncturing of the apexby the delivery system, the felt is firmly attached to the heart suchthat the apex is centrally located. Secondarily, the delivery system isintroduced through the central area, or orifice as it may be, of thepledget. Positioned and attached in this manner, the pledget acts tocontrol any potential tearing at the apex.

In another embodiment the valve can be seated within the valvularannulus through the use of tines or barbs. These may be used inconjunction with, or in place of one or more tethers. The tines or barbsare located to provide attachment to adjacent tissue. In someembodiments, the tines are optionally circumferentially located aroundthe bend/transition area between frame body 144 and the cuff 146. Suchtines are forced into the annular tissue by mechanical means such asusing a balloon catheter. In one non-limiting embodiment, the tines mayoptionally be semi-circular hooks that upon expansion of the frame body,pierce, rotate into, and hold annular tissue securely.

One embodiment of an inner frame 100 is shown in side view in FIG. 2 .Frame 100 includes a cylindrical framework 102 defining a lumen 104, andincluding three generally diamond-shaped members 106, 108, 110. Eachdiamond-shaped member is directly connected to, or has at least oneconnecting member 120 connecting to, each of the other twodiamond-shaped members. Spanning members 122 cross the open span of thediamond-shaped members and provide a strengthening structuralenhancement, another sewing anchor location for the other components ofinner assembly 12, or both.

Another embodiment of inner frame 100 is shown in side view in FIG. 3 .This embodiment includes optional valve sewing rings 105 and tetherattachment structures 111. Each valve sewing ring 105 provides anaperture for sewing the leaflet tissue structures to the wire framework100.

Another embodiment of inner frame 100 is shown in an opened andflattened view in FIG. 4 . This view is intended primarily forillustrative purposes of the wireframe structure, since the manufactureof the cylindrical framework will generally be made from a laser-cutpiece of Nitinol® tubing that is expanded to form a larger cylindricalstructure, and the wireframe structure will generally not bemanufactured from a rolled-up welded metal lattice. FIG. 4 shows eachdiamond-shaped member defining two lateral vertices 112 and 114 and twolongitudinal vertices 116 and 118. Each diamond-shaped member isdirectly connected to, or has at least one connecting member 120connecting to, each of the other two diamond-shaped members. Theconnecting members defined in this embodiment as joined legs 126, 128connected at a V-shaped connecting vertex 124. FIG. 4 also showsspanning members 122 crossing the open span of the diamond-shapedmembers and providing a strengthening structural enhancement, anothersewing anchor location, or both. FIG. 4 shows point A and point B, whichare the locations at which the connecting members are joined to form acylindrical structure (or said another way, the location at which thetubular inner frame 100 is cut to be opened up and flattened for theview shown in FIG. 4 ).

Another embodiment of an inner frame, in this instance designated 200,is shown in FIG. 5 in a flattened view. Inner frame 200 includes acylindrical framework 202 defining a lumen 204. As in FIG. 4 , this viewin FIG. 5 is intended primarily for illustrative purposes of thewireframe structure, and point A and point B designate the locations atwhich the wireframe is joined to form a cylindrical structure.

Another embodiment of an inner frame, in this instance designated 300,is shown in flattened view in FIG. 6 . Inner frame 300 includes threediamond-shaped members, not having spanning members. Cylindricalframework 302 defines a lumen 304 using each of diamond-shaped members306, 308, and 310. FIG. 6 again shows point A and point B, which are thelocations at which the connecting members are joined to form acylindrical structure.

Another embodiment of an inner frame, in this instance designated 400,is shown in side view in FIG. 7 . This four-diamond embodiment includesa cylindrical framework 402 defining a lumen 404, in which cylindricalframework 402 includes four generally diamond-shaped members.

A flattened view of another four-diamond embodiment of inner frame 400is shown in a flattened view in FIG. 8 . FIG. 8 shows diamond-shapedmembers 406, 407, 408, and 409, each having joining legs, shown for 406as joining components (legs) 426 and 428, which define vertices, such asthat shown at joined end 432. FIG. 8 also shows spanning members, suchas that shown at 422, crossing the open span of the diamond-shapedmembers and providing a strengthening structural enhancement, anothersewing anchor location, or both. FIG. 8 again shows point A and point B,which are the locations at which the connecting members are joined toform a cylindrical structure.

Another embodiment of an inner frame, in this instance designated 500,is shown in flattened view in FIG. 9 . Inner frame 500 includescylindrical framework 502 defining lumen 504.

Another embodiment of an inner frame, in this instance designated 600,is shown in flattened view in FIG. 10 . Inner frame 600 includescylindrical wireframe 602 defining a lumen 604 using diamond-shapedmembers 606, 607, 608, and 609. Each diamond-shaped member is joined ata connecting point, such as that shown at 628.

Another embodiment of an inner frame, in this instance designated 700,is shown in side view in FIG. 11 and in flattened view in FIG. 12 . Thisembodiment has three square-shaped members connected by a v-shapedjoining element. Square-shaped members 706, 708, and 710, each have av-shaped joining element, such as that shown as 724. Inner frame 700also includes lateral vertices 712, 714 and longitudinal vertices 716,718 and spanning members, such as that shown at 722, crossing the openspan of the square-shaped members and providing a strengtheningstructural enhancement, another sewing anchor location, or both. Again,point A and point B are the locations at which the integral connectingmembers make their connection to form a cylindrical structure.

Another embodiment of a prosthetic valve is shown in exploded view inFIG. 13 . Valve 10′ also includes an inner structure or assembly 12 andan outer structure or assembly 14. Valve 10′ may also be coupled to atether 160 and a tether anchor 154.

Inner assembly 12 includes inner frame 302, outer cylindrical wrap 152,and leaflet structure 136 (including articulating leaflets 138 thatdefine a valve function). As in the embodiment in FIG. 1 , leafletstructure 136 may be sewn to inner frame 302, and may use parts of innerframe 302 for this purpose. Inner assembly 12 is disposed within andsecured within outer assembly 14.

Outer assembly 14 includes outer frame 144. Outer frame 144 may alsohave in various embodiments an outer frame cover of tissue or fabric(not pictured), or may be left without an outer cover to provide exposedwireframe to facilitate in-growth. Outer frame 144 has an articulatingcollar or cuff 147 is covered by cover 148 of tissue or fabric. Cuff 147may also have in some embodiments a vertical A2 section to accommodateand solve left ventricular outflow tract (LVOT) obstruction issues.

In this embodiment, tether 160 is connected to valve 10′ by outer frame144, in contrast to the embodiment in FIG. 1 , in which the tether isattached to valve 10 by inner frame 100. To implement this alternativetether attachment, in this embodiment, outer frame 144 also hasattachment members or struts 113. A tether anchor 156 can be attached tothe lower ends of the struts, and tether 160 can be attached to tetheranchor 156. In this embodiment, tether 160 can be connected toepicardial securing pad 154.

An embodiment of an outer frame 144 having attachment members or struts113 is shown in FIGS. 14A to 14C. In this embodiment, outer frame 144 isformed from a milled or laser-cut tube of Nitinol®. FIG. 14A shows thetube as initially milled or laser cut, i.e. before deformation. The tubecan be divided into four portions, corresponding to functionallydifferent portions of the outer frame 144 in final form: cuff portion246, frame body portion 245, strut portion 243, and tether connectingportion 242. Strut portion 243 includes six struts 213, which connectbody portion 245 to tether clamp portion 242. Connecting portion 242includes longitudinal extensions of struts 213, connectedcircumferentially by pairs of opposed, slightly V-shaped connectingmembers (or “micro-Vs”). Connecting portion 242 is configured to beradially collapsed by application of a compressive force, which causesthe micro-Vs to become more deeply V-shaped, with the vertices movingcloser together longitudinally and the open ends of the V shapes movingcloser together circumferentially. In one embodiment, connecting portion242 can be configured to compressively clamp or grip one end of atether, either clamping directly onto a tether line (e.g. braidedfilament line) or onto an intermediate structure, such as a polymer ormetal piece that is in term firmly fixed to the tether line. In anotherembodiment, connecting portion 242 can be coupled to a tether by amechanical connection (e.g. stitches, pins, etc.), an adhesiveconnection, or any other suitable technique. In some embodiments, butclamping and one or more other connection techniques can be used incombination.

In contrast to connecting portion 242, cuff portion 246 and body portion245 are configured to be expanded radially. Strut portion 243 forms alongitudinal connection, and radial transition, between the expandedbody portion and the compressed connecting portion 242. FIG. 14B showsouter frame 244 in a partially deformed configuration, i.e. withconnecting portion 242 compressed to a slightly smaller radial dimensionthan the initial configuration in FIG. 14A, and with cuff portion 246and body portion 245 expanded to a slightly larger radial dimension.FIG. 14C shows outer frame 244 in a further partially deformed (thoughnot fully deformed to the final, deployed configuration).

Another embodiment of a prosthetic valve is shown in exploded view inFIG. 15 . Valve 10″ also includes an inner structure or assembly 312 andan outer structure or assembly 314. Valve 10″ may also be coupled to atether 360 and a tether anchor 354.

Inner assembly 312 includes inner frame 340, outer cylindrical wrap 352,and leaflet structure 336 (including articulating leaflets 338 thatdefine a valve function). As in the embodiment in FIGS. 1 and 13 ,leaflet structure 336 may be sewn to inner frame 340, and may use partsof inner frame 340 for this purpose. Inner assembly 312 is disposedwithin and secured within outer assembly 314, as described in moredetail below.

Outer assembly 314 includes outer frame 370. Outer frame 370 may alsohave in various embodiments an outer frame cover of tissue or fabric(not pictured), or may be left without an outer cover to provide exposedwireframe to facilitate in-growth. Outer frame 370 may also have anarticulating collar or cuff 347 covered by cover 348 of tissue orfabric.

In this embodiment, tether 360 is connected to valve 10″ by inner frame340, similar to the embodiment in FIG. 1 , but employing the connectingportion and strut portion features of the outer frame 144 of the valve10′ in FIG. 13 . Thus, inner frame 340 includes tether connecting orclamping portion 344 by which inner frame 340, and by extension valve10″, is coupled to tether 360.

Inner frame 340 is shown in more detail in FIGS. 16-18 . Inner frame 340can be formed from a milled or laser-cut tube of, for example, Nitinol®.Inner frame 340 is illustrated in FIG. 16 in an undeformed, initialstate, i.e. as milled or laser-cut, but cut and unrolled into a flatsheet for ease of illustration. Inner frame 340 can be divided into fourportions, corresponding to functionally different portions of the innerframe 340 in final form: apex portion 341, body portion 342, strutportion 343, and tether clamp portion 344. Strut portion 343 includessix struts, such as strut 343A, which connect body portion 342 to tetherclamp portion 344.

Connecting portion 344 includes longitudinal extensions of the struts,connected circumferentially by pairs of micro-V's. Similar to connectingportion 242 of outer frame 244 in FIGS. 14A-C, connecting portion 344 isconfigured to be radially collapsed by application of a compressiveforce, which causes the micro-Vs to become more deeply V-shaped, withthe vertices moving closer together longitudinally and the open ends ofthe V shapes moving closer together circumferentially. Thus, connectingportion 344 can clamp or grip one end of a tether, either connectingdirectly onto a tether line (e.g. braided filament line) or onto anintermediate structure, such as a polymer or metal piece that is in termfirmly fixed to the tether line. Other techniques can be used to connecta tether to connection portion 344, as discussed above for connectionportion 242 of outer frame 244.

In contrast to connecting portion 344, apex portion 341 and body portion342 are configured to be expanded radially. Strut portion 343 forms alongitudinal connection, and radial transition, between the expandedbody portion and the compressed connecting portion 344.

Body portion 342 includes six longitudinal posts, such as post 342A. Theposts can be used to attach leaflet structure 336 to inner frame 340,and/or can be used to attach inner assembly 312 to outer assembly 314,such as by connecting inner frame 340 to outer frame 370. In theillustrated embodiment, the posts include openings through whichconnecting members (such as suture filaments and/or wires) can be passedto couple the posts to other structures.

Inner frame 340 is shown in a fully deformed, i.e. to the final,deployed configuration, in side view and bottom view in FIGS. 17 and 18, respectively.

Outer frame 370 of valve 10″ is shown in more detail in FIGS. 19-21 .Outer frame 370 can be formed from a milled or laser-cut tube of, forexample, Nitinol®. Outer frame 370 is illustrated in FIG. 19 in anundeformed, initial state, i.e. as milled or laser-cut, but cut andunrolled into a flat sheet for ease of illustration. Outer frame 370 canbe similar to outer frame 144 described above in connection with valves10 and 10′. Outer frame 370 can be divided into a coupling portion 371,a body portion 372, and a cuff portion 373, as shown in FIG. 19 .

Coupling portion 371 includes multiple openings or apertures, such as371A, by which outer frame 370 can be coupled to inner frame 340, asdiscussed in more detail below.

In this embodiment, cuff portion 373 includes an indicator 374. In thisembodiment, indicator 374 is simply a broader portion of the wire frameelement of cuff portion 373, i.e. Indicator 374 is more apparent onradiographic or other imaging modalities than the surrounding wire frameelements of cuff portion 373. In other embodiments, indicator 374 can beany distinguishable feature (e.g., protrusion, notch, etc.) and/orindicia (e.g., lines, markings, tic marks, etc.) that enhance thevisibility of the part of cuff portion 373 on which it is formed, or towhich it is attached. Indicator 374 can facilitate the implantation ofthe prosthetic valve by providing a reference point or landmark that theoperator can use to orient and/or position the valve (or any portion ofthe valve) with respect to the native valve or other heart structure.For example, during implantation, an operator can identify (e.g., usingechocardiography) the indicator 373 when the valve is situated in apatient's heart. The operator can therefore determine the locationand/or orientation of the valve and make adjustments accordingly.

Outer frame 370 is shown in a fully deformed, i.e. to the final,deployed configuration, in side view and top view in FIGS. 20 and 21 ,respectively. As best seen in FIG. 21 , the lower end of couplingportion 371 forms a roughly circular opening (identified by “O” in FIG.21 ). The diameter of this opening preferably corresponds approximatelyto the diameter of body portion 342 of inner frame 340, to facilitatecoupling of the two components of valve 10″.

Outer frame 370 and inner frame 340 are shown coupled together in FIGS.22-24 , in front, side, and top views, respectively. The two framescollectively form a structural support for a prosthetic valve such asvalve 10″ in FIG. 15 . The frames support the valve leaflet structure inthe desired relationship to the native valve annulus, support thecoverings for the two frames to provide a barrier to blood leakagebetween the atrium and ventricle, and couple to the tether (by the innerframe 340) to aid in holding the prosthetic valve in place in the nativevalve annulus by the tether connection to the ventricle wall. The twoframes are connected at six coupling points (representative points areidentified as “C”). In this embodiment, the coupling points areimplemented with a mechanical fastener, such as a short length of wire,passed through aperture (such as aperture 371A) in coupling portion 371of outer frame 370 and corresponding openings in longitudinal posts(such as poste 342A) in body portion 342 of inner frame 340. Inner framestructure 340 is thus disposed within the outer frame 370 and securedcoupled to it.

While various embodiments have been described above, it should beunderstood that they have been presented by way of example only, and notlimitation, and as such, various changes in form and/or detail may bemade. Any portion of the apparatus and/or methods described herein maybe combined in any suitable combination, unless explicitly expressedotherwise. Where methods and/or schematics described above indicatecertain events occurring in certain order, the ordering of certainevents and/or flow patterns may be modified. Additionally, certainevents may be performed concurrently in parallel processes whenpossible, as well as performed sequentially.

What is claimed:
 1. A method of manufacturing a prosthetic heart valve,comprising: forming an outer frame of a shape memory alloy; forming aninner frame of a shape memory alloy, the inner frame having a firstportion and a second portion; coupling the outer frame to the innerframe; coupling a prosthetic leaflet assembly to the first portion ofthe inner frame; and compressing the second portion of the inner frameover a first end of a tether.
 2. The method of claim 1, wherein theshape memory alloy of the outer frame is a nickel-titanium alloy.
 3. Themethod of claim 1, wherein the shape memory alloy of the inner frame isa nickel-titanium alloy.
 4. The method of claim 1, wherein the outerframe is coupled to the inner frame by one or more mechanical fasteners.5. The method of claim 1, wherein the outer frame is formed separatelyfrom the inner frame.
 6. The method of claim 1, wherein after couplingthe outer frame to the inner frame, a distal end of the outer frame isdisposed distal to a distal end of the inner frame.
 7. The method ofclaim 1, wherein the inner frame is formed into an initial shape, andthe first portion of the inner frame is expanded from the initial shape,wherein compressing the second portion of the inner frame includescompressing the second portion of the inner frame from the initialshape.
 8. The method of claim 7, wherein after compressing the secondportion of the inner frame, the second portion of the inner framedefines a lumen having a width and a length that is greater than thewidth.
 9. The method of claim 1, wherein after compressing the secondportion of the inner frame over the first end of the tether, the secondportion of the inner frame is disposed circumferentially continuouslyaround the first end of the tether.
 10. The method of claim 1, whereinthe inner frame defines a central axis, and after compressing the secondportion of the inner frame over the first end of the tether, the secondportion of the inner frame is disposed along the central axis.
 11. Themethod of claim 1, wherein forming the inner frame includes forming thesecond portion of the inner frame to include a plurality of “V”-shapedstrut members, and compressing the second portion of the inner frameincludes causing vertices of adjacent “V’-shaped strut members to movecloser together longitudinally, and causing open ends of individual onesof the “V” shaped strut members to move closer togethercircumferentially.
 12. The method of claim 1, wherein compressing thesecond portion of the inner frame over the first end of the tetherincludes compressing the second portion of the inner frame directly ontothe first end of the tether.
 13. The method of claim 1, whereincompressing the second portion of the inner frame over the first end ofthe tether includes compressing the second portion of the inner frameonto an intermediate structure between the second portion of the innerframe and the first end of the tether.
 14. The method of claim 13,wherein the intermediate structure is a polymer or metal piece.
 15. Themethod of claim 1, further comprising additionally coupling the secondportion of the inner frame to the first end of the tether by amechanical connection.
 16. The method of claim 15, wherein themechanical connection includes sutures.
 17. The method of claim 15,wherein the mechanical connection includes pins.
 18. The method of claim1, further comprising additionally coupling the second portion of theinner frame to the first end of the tether by an adhesive.
 19. Themethod of claim 1, wherein the inner frame is formed from a tube of theshape memory alloy.
 20. The method of claim 1, wherein the outer frameis formed from a tube of the shape memory alloy.